Water-soluble organic compound of arsenic and process of producing it



Patented July 17, 192 8.

UNITED STATES PATENT OFFICE.

MORRIS 8. KHARASCH, OF COLLEGE PARK, INDIANA.

WATER-SOLUBLE ORGANIC COMPOUND OF ARSENIC AND PROCESS OF PRODUCING IT.

No Drawing.

Thd present invention relates to watersoluble organic arsenious compounds, in which the arsenic is bonded by one bond to a carbon atom of an organic radical; and to the process of producing such water-soluble organic arsenious com unds.

More specifically, t e water-soluble or- 'ganic arsenious compounds which are produced by my invention have the arsenic atom bonded by one bond to a carbon atom of an organic radical, and have the arsenic atom" bonded by its two remaining bonds to sulphur atoms, and have each sulphur atom bonded to a carbon atom of an or nic radical containin an acid group whic as a free valence bon capable of being attached either to hydrogen or to a metal. While my invention contemplates that the first-named organic radical shall be either an aliphatic or an aromatic radical. yet I prefer that it be an aromatic radical, specifically a phenyl radical, and desirably that it be a substituted aromatic radical, and specifically a substituted phenyl radical in which one or more of the hydrogen atoms of the phenyl group have been replaced by an amine group or groups, and/or by a hydroxyl group or groups, and/or by a substituted amine or hydroxylgroup or grou s. The or anic radical bonded to the sulp ur may be either aliphatic or aromatic.

In the past, organic compounds of trivalent arsenic have found very limited a plication as therapeuticagents, due to t e fact that they are insoluble in water, and are even insoluble inan alkali solution ,unless the alkalinit of the solution is very great. Illustrations of such known organic com pounds of trivalent arsenic are:

1) Phenyl arseuious oxide:

(2) P-amino phenyl arseniousoxide:

Application filed January 22, 1827. Serial No. 162.925.

These compounds while soluble in strong sodium hydroxide solution to give the salts 0-No 0-Na A o-m on large extent.

bus, while derivatives of organic compounds of pentavalent arsenic have found considerable application as general therapeutic agents, especially as antisyphilitics, the organic compounds of trivalent arsenic, although enormously more efl'ective, have not met with any degree of success and have gepsrally been regarded as an unpromising By my invention, I make organic compouiidsoftrivalent arsenic efiectivel available, for uses generally similar to t ose of or anic compounds of pentavalent arsenic.

n my Patent No. 1,589,599, granted June 22, 1926, I describe a general method Whereby organo-metallic compounds can be introduced into water solution by the use of acids containin sulfhydryl groups; includin tliioglyco ic acid, B-sulfh dryl butyric aci thiomalic acid, thiosalicycl ic acid,sulfhydryl benzene sulfonic acid, mercapto benzothiazole carboxylic acid, and substitution prodnets of such acids, aswell as other compounds containing a sulfhydryl (-SH) group or groups and an acidic group or groups such as the carboxylic roup (COOH) or the sulfonic group (-S8,H).

ill

That patent, although including claims covering generically certain water-soluble organo-metallic compounds and the process of producing them when the metal M therein referred to has a valence greater than one, and although giving an arsenic compound as one example of such 'generic type of compounds, was directed in its more specific claims to mercury compounds; so that claims directed specifically to arsenic compounds could not be obtained therein. This present application, on the other hand, is directed specifically to arsenic compounds; and while its more generic claims include the potassium salt of phenyl arscnious thioglycollic acid described in my prior patent, since that compound could not be claimed specifically GOOH I NH:

This is a compound which is readily soluble in sodium bicarbonate solution, and is solable in the calculated amount of sodium hydroxicle solution. In either case, the sodium CODE ( coon m RAs=Y.

in which R is any organic radical having a carbon atom directly attached by one bond to the arsenic, and Y is a non-metallic divalent atom dther than of the sulphur family (in which family I mean to include sulphur,

in that patent the more specific claims of the present application are directed to substituted-aromatic trivalent-arsenic thio-acid compounds, especially to substituted-phenyl trivalent-arsenic thio-acidcompounds, and

COOH

S COOH 11 0 S OOONa selenium, and tellurinm and theseonly) or two non-metallic monovalent atoms. The organic radical which It represents may broadly be any organic radical of the ali phatic or iaromatic series; but I prefer that it be an aromatic radical, such as the phenyl group, and that this aromatic radical be a substituted aromatic radical. such as a sub stituted phenyl group; and in some cases it seems better that Y be a single atom of oxygen, rather than two atoms of chlorine, for instance, so that the final compound will be formed With the setting; free of water only rather than of a halogen acid; in which case the initial arsenic compound would be of the general formula RAs=0.

For the thio acid used in the process. the general formula is HSR -H in which R is an aromatic or aliphatic organic radical having a carbon atom attached to the sulfhydryl group and also containing an acid group which has a free valence bond capable of being attached either to hydrogen to form the acid, as shown, or to :1 meta to This would give a radical of the form a salt of such acid. a final product containing following typical formula:

flR

In this final product, the arsenic atom is directly bonded by one bond to a carbon atom of the radical R, and is di rectly bonded by two bonds to sulphur atoms; and each sulphur atom is directly bonded by one bond to a carbon atom of an organic radical which contains an acid group such as above defined; so that such product, by the substitution of sodium or otassium for hydrogen at the free bond the acid group, permits the preparation of a sodium or potassium salt soluble in water.

Indeed, I prefer to use the sulfhydryl sulfonic acids as the thio acids. These have (8) RAs the advantage in that when they react with As-O The acid roduced by the above reaction is water solu le; and the solution of it may be iven varying hydrogen ion concentrations %y the addition of varying amounts of an alkali.

The effective compound thus produced thus contains a radical of the following general formula in which R may be a suitable organic radical combinable with the S0 group to form a sulfonic acid. The radical shown in formula 10 is merely emore specific example of the radical shown in formula 8. 7

Further, if sulfhydryl sulfonic acids are used containing two sulfonic acid groups, such as Q-sulfhydryl-na hthyl-G; S-disulfonic acid, it is possible to o tain final soluble arwith those other thin acids the acid formed by the reaction of the initial trivalent arsenic compound with the initial thio acid produces acids which are themselves not usually materially soluble in water, so that it is necessary to reduce salts thereof in order to get the desired water solubilit In consequence, by using sulfhydryl su fonic acids, it is possible to get an aqueous solution of any desired hydrogen ion concentration Within a wide range extending cnboth sides of the neutral point.

Thus, if instead of using thiosalic'ylic acid in the reaction shown in equation (5), one uses p-sulfhydryl benzene sulfonic acid, instead of the reaction shown in equation (5), one would get the following reaction:

s-Osolfi v NH:

l Ewample 1.

To 10.5 grams of p-dimethyl amino phenyl arsenious oxide suspended in 75 c. c. of alcohol is added a solution in alcohol of 15.4 grams of thiosalicylic acid. (Alcohol is not the only suitable solvent, as other solvents, such as acetone, may also be used.) The mixture .is shaken for a while, and the pdimethyl amino phenyl arsenious oxide goes into solution, with the following reaction:

coon

- 8 11 000B coon The reaction mixture is usually warmed for about five minutes at 40-50 (1., and, if then not completely clear, is filtered. It is then treated with water, and cooled thoroughly. A precipitate separates, which is p-dimethyl amino phenyl arsenious thiosalicylic acid, having the formula of the first term on the right-hand side of the foregoing reaction equation. This precipitate is collected on a filter, washed well with water to remove any alcohol, and dried in a dessicator. This compound as ordinarily obtained is a faintly yellow crystalline substance which decomposes at slightly below 100. It is soluble in alcohol and in ether. It is readily soluble in either sodium bicarbonate or sodium hydroxide to a practically neutral reaction, which makes it suitable, for intravenous injection; Whereas the p-dilnethyl amino phenyl arsenious oxide is only soluble in strong sodium hydroxide solution, too alkaline for intravenous or subcutaneous use, and is practically insoluble either in sodium bicarbonate or sodium carbonate. In this (13) AQO NHCOCH! coon (OOH 2NaHCO:

NHCOCH:

The sodium salt of p-acetyl amino phenyl arsenious'thiosalicylic acid thus formed is soluble in Water. A solution of this sodium salt,.when injected intravenously, shows marked trypanocidal activity.

COOH

neutral solution, the sodium has replaced the hydrogen of the acid, to form the following water-soluble sodium salt:

COONa S COONa Emample 2.

To 11.2 grams of p-acetyl amino phenyl arsenious oxide suspended in 75 c. c. of al (ohol is added an alcoholic solution of 15.4 grams of thiosalicylie acid. The mixture is warmed very gently to 5060 C. The pacetyl amino phenyl arsenious oxide goes into solution, with the following reaction:

COOK /6. r

NHCOCHI of the first term on the right-hand side of" the reaction equation just given. It is a very light yellow crystalline substance. It melts at about 216 to 219 C. It is soluble in alcohol. When treated with sodium bicarbonate solution, it dissolves readily, the following reaction taking place:

coons Aa a SCOONB Z'HzO-l-ZCO:

NHCOCHI Ewample 3.

oxide dihydrate,

NKPO'AIO- (mo) 1,

dissolved in a small volume of alcohol or acetone, is added gradually with stirring a concentrated alcoholic solution of 6.16 grams of thiosalicylic acid The mixed solution is warmed a few minutes at to 60 C., and then allowed to stand a few hours at room temperature. The following reaction takes place:

ooon

s .a( 000K 8 COOH NH: NH: COONa On concentrating at a low temperature a precipitate separates out, which is p-amino phenylarsenious thiosalicylic acid, having the structural formula of the first term on As the right-hand side of the foregoing reacg 000M tion equation. This precipitate may also be obtained by adding water to the alcoholic (16) solution.

This precipitate is collected on a filter, NH

washed with a little cold alcohol and water, and dried. As ordinarily obtained by the above method, this compound is a pale yellow crystalline substance which when rapidly heated turns brown at about 130 (3., and which melts with decomposition at 145160 6., depending on the rate of heating. If heated for severai hours at 110 C. it decomposes into a brown tarry mass.

P-amino phenylarsenious thiosalicylic acid is practically insoluble in water, ether, and concentrated hydrochloric acid. It is slightly soluble in dilute hydrochloric acid, and readily soluble in dilute alkalis, alcohol, and acetone. It forms water-soluble salts with the alkali metals such as sodium and potassium, with ammonia, and with the alkaline earths such as calcium. The structural formula of the sodium salt As-O + 2 nsO-eoaa NHOOOHa 80 ous sulpho benzene sulphorrio acid having A solution of the sodium salt of p-amino phenylarsenious thiosalicylic acid, when injected intravenously, shows a marked trypanocidal activity.

Emmnple 4. To 2.43 grams of p acetyl amino phenyl arsenious oxide monohydrate,

CH CONH AS O-HzO,

suspended in 50 cc. alcohol, is added gradually with stirring an alcoholic or aqueous solution containing 3.80 grams of p-sulfhydryl benzene sulphonic acid,

SOaH O H20. SOiH NHOOCH:

the structural formula as indicated in the first term on the right-hand side of the foregoing reaction equation. \Vhen the reaction has been completed, the precipitate is 001- V lceted on a filter, washed with alcohol. and dried in vacuo.

The p-aeetyl amino phcnyl arscnious sulpho benzene sulphonic acid is a pale cream or white crystalline substance which does not melt or darken when heated to 300 C. It is :omewhat soluble in water and in dilute hydrochloric acid. can he precipitated from a saturated aqueous solution by the addition of concentrated hydrochloric acid. is readily soluhle in-dilute alkali. is sl ghtly soluhle in alcohol-and acetone. and is insoluble in ether. It forms water-soluhle salts with the alkali metals such as sodium and potassium. with ammonia. and with the alkaline-earth metals such as calcium. The structural formula of the sodium salt is:

Ewan/pie 5.

To 1: 'rams of p-acctyl amino phcnyl ea rsemous oxide monohydratc.

cnscoNn-O-xs -n1o,

dissolved in, T c. c. of arm ethyl alcohol. is added a concentrated solution of 1.70 gram. of cysteine hydrochloride in water or alcohol. After a few minutes stirrin c a re- S S03N1t (is) CH CONE action is indicated by the tact that a precipia i tate begins to form. The following reaction O takes place scmcncwmaoucoon As=O s somcncumncooooa ns-cm (1 2 dnnmnci mo.

0011 i in-cocni NHtOCHa After standing 24 hours at room temperature. the white crystalline precipitate having the structural formula shown in the first term on the right hand side of the foregoing reaction equation. is filtered 011' and washed with alcohol and dried in vacuo. It decomposes at 196-198 C. with foaming. This compound is soluble in water. in concentrated hydrochloric acid. and in dilute alkali. It is slightly soluble in alcohol. and insoluble in acetone and ether. It forms water-soluble salts with the alkali metals such as sodium and potassium. with ainmonia, and with the alkaline-earth metals such as calcium. The. formula for the sodium salt is SCH:CH(NII1)COON8 CH;CONH- 'As scmoamnacoom (2 2 nscazonicooa NHCOGH:

The product of the reaction. p-acetyl amino phenyl arsenious sulfo-propionic acid. having the structural formula. of the first term on the right-hand side of the foregoing reaction equation. is soluble in alcohol. and so may he isolated as follows :The alcoholie solution is concentrated to a small volume, and water is added. whereupon a precipitate forms. This precipitate is filtered A solution of this sodium salt shows a marked tIyptUlUClFl'rll activity. and less toxic than that amount of the arscnions oxide which contains an equal quantit of arsenic.

Example 6.

To 1.22 grams of p-acetyl amino phenyl arsenious oxide monohydrate.

cmcoNnOAsoin l NHCOCH:

ofl', dried. and then suspended in ether, from which it is obtained by filtration as a pale yellow or white powder, melting; at

120-126 The reaction product also may be obtained by evaporating the alcohol until a curdy residue remains. at which point. ether is added and the insoluhle portion collected on a. filter. washed with ether. and dried.

The p-acetyl amino phenyl arsenious sulequation. E small volume, further amounts of the fo-propionic acid, of-the foregoing formula, is soluble in.warm water, in alcohol, in ace tone, and in dilute alkali, but is insoluble in concentrated hydrochloric acid and in ether. It forms w tar-soluble salts with the alkali metals such as sodium and potassium, and with ammonia. The calcium salt is but slightly soluble in water.

The formula for the sodium salt is or; CfhCOONa (22) CHzCONHO-A s-cincmooom A solution of the sodium salt of p-acetyl amino phenyl arsenious sulfo-propionic acid shows a marked trypanocidal activity, and is less toxic than an amount of the tar senious oxide containing the same quantity of arsenic.

As-O

+ ans-Oomooon NHOOGH! On cooling a pale yellow colored precipitate forms, which is p-acetyl amino phenyl arsenious sulfo phenyl acetic acid, having the structural formula of the first term on the right hand side of the foregoing reaction Upon evaporating the alcohol to p-acetyl amino phenyl arsenious sulfo phenyl acetic acid are separated from the solution. The reci itate is collected on a filter, washed wit co d alcohol, and dried. The compound as ordinarily obtained from the above described-reaction is a'pale yellow crystalline substance, which may be further :4 CHgCONH-OA A solution of the sodium salt of p-acetyl amino phenyl arsenious sulfo hcnyl acetic acid shows a marked trypanocidal activity, and is less toxic than an amount of the arsenious oxide containing the same quantity of arsenic.

Earample 8. To 2.20 ams of p-amino phenyl arsenious oxide ihydrate,

The precipitate which separates is pamino phenyl arsemous cysteine hydro- E'mample 7. 20

To 1.22 grams of p-acetyl amino phenyl arsenious oxide monohydrate,

suspended or dissolved in a suitable amount of alcohol, (2575 c. c.) is added with stirring a .concentrated alcohol solution of 1.68 gms. of p-sulfhydryl phenyl acetic acid,

nsOcmooon.

The combined alcoholic solutions remain clear, and are warmed a few minutes at 50 35 to 60 C. The following reaction takes place:-

Oomooorr -oa.oooa 11.0,

NHOOOHs NHr- AsO- anon,

dissolved in 25 to 50 Cfic. of warm alcohol, is added gradually with stirring a concentrated alcoholic solution of 3.40 grams cysteine hydrochloride. A white precipitate forms during this addition, indicating that a reaction has taken place. The following equation represents this reaction NH] chloride, having the formula of the first term on the right hand side of the foregoing reaction e nation. This precipitate is collected on a lter, washed with a little alcohol, and dried in vacuo. The compound as ordinarily obtained is a white crystalline substance, which darkens when heated to 1601(55 C., and decomposes when heated to hi her temperatures.

t, is soluble in water with an acid reaction, giving a precipitate on neutralizing. It is also soluble in dilute alkali, dilute acid, and concentrated hydrochloric acid; it is slightly soluble in alcohol and acetone, and is insoluble in ether. It forms \\ate1soluble salts with the alkali metals such as sodium and potassium, with ammonia, and with the alkaline-earth metals'such as calcium. The structural formula of the sodium salt is A solution of the sodium salt of pamino phenyl arsenious cysteine shows a marked trypanocidal activity.

Example .9.

To 1.567 grams of 4-hydroxy 3-amino phenyl arsenious oxide.

trated aqueous solution containing 3.4 guns. of p-sulfhydryl benzene sulfonic acid,

HsOsoin.

(Ether alcohol or acetone may be used as solvents instead of water). The formation of a white precipitate is evidence of the fact that a reaction has occurred; which is as follows A SCHzCH(NH1)COONB SCHICH NHI)COONB AFC . I NH/ NH This precipitate, which is 4-hydroxy 3- amino phenyl arsenious sulfobenzene sulfonicacid having the structural formula of the first term on the right-hand side of the foregoing reaction equation. is collected on a filter, washed with a little water and dried. The compound as ordinarily obtained by the above method is a white or pale yellow crystalline substance, which melts with decomposition at 265280 C., the exact temperature depending upon the rate of heatin 1t is soluble in water, dilute acids, and alkalis, slightly soluble in alcohol and acetone, and insoluble in ether. It forms water-soluble salts with the alkali metals such as sodium or potassium, with ammonia, and with the alkaline-earth metals such as calcium. The structural formula, of the sodium salt is:--

s SO=Na 04 s-Osoma E wample 10; To 1.63 grams of i-hydroxy 3-amino phenyl arsenious oxide,

dissolved in a small quantity of water. is

added gradually with stirring an alcoholic solution of 2.55 grams of thiosalicylic acid,

The following reaction takes places The solution is warmed a few minutes at to C. to complete the reaction and then concentrated to a small volume,w ereupon a precipitate forms; whichcontains 4 hydroxy 3-arnino phenyl arsenious thiosalicylic acid, having the structural formulagof stance, having an indefinite meltingij decomposing when heated. It is inso u water and in ether, and iii-moderately soluble in alcohol and inacetone. .It is soluble in dilute, alkali. I salts with thealkalimetals sucha dium or potassium, with ammonia, and with the :11 ka ine-ea'rth metals such as calcium. The structural formula of sodium salt is coon.

NH: I (so) O GOONI a cohol, acetone, and other. It forms water sodium and The. formula for the sodium M11318?- Ksoar-cnmaecoom (m SOHr-CfIWHnlCOONa A solution of the sodium salt of p-hy- It forms wate soluble h 'drochlo'ric' acid. It is insoluble in ethyl I the first term on the right-hand side of the foregoin reaction equation, This precipitate is co lected on a filter, washed with water and dried.

The compound as ordinarily obtained by. the above method is a cream-colored sub int,f g A solution of the sodium salt of 4-hydroxy shows a marked trypanocidal activity, and

3'-amino phenyl arsenious thiosalicylic acid is less toxic than an amount of the arsenious 35 oxide contammg'the same quantity of arsemc. 1* 1;

Example 11 a a 0.242 grains of p hydroxyphenyl arsine 40 no-O-uo dissolved in 10 c. c. of ethyl alcohol, is added 4 a solution of 0.42 ams of cysteine hydrochloride in ethylafi ohol. After a few minutes stirringa reaction is indicated by the formation of a flocculent precipitate. The following reaction takes place zom onmmucncoon cm-osmkmcucooa oxide,

droxyphenyl arsenious cysteine shows a marked trypanocidal activity.

Example 12.

CHlCONH I WO an (prepared by'reducing 3-amino 4 hydroxy- 1 phenyl arsonic acid with S0, in the presence of H1 to fi-amino 4-hydroxy phenyl arsenious oxide, and acetylating the amino group the water bath until it is so. The following reaction takes place M omomooor aomomoooa- (3 +2Hsomomooon omoomi The product of the reaction, 3-acet'ylamino 4-hydroxyphenyl a'rsenious sulfopropionic acid, having the structural formula of the first term on the right hand side of the foregoing reaction equiftion, being soluble in alcohol, may be isolated as follows :'The alcoholic solution is concentrated to a small volume, and ether is added, whereupon a' precipitate'forms.

This precipitate is filtered' ofl", washed with ether, and dried. The product as usually obtained is a pale yellow or white solid melting at 140,144 C.

The 3-acetylamino- 4-h droxyphenyl arsenious sulfopropionic aci is somewhat soluble in water, andin dilute hydrochloric acid. It is readily soluble in dilute alkali, alcohol, and acetone, and is almost insoluble n ether. It forms water -soluble saltsiwith the alkali metals such as sodium and potassium, with ammonia, and with calcium. The formula for the sodium salt is CH:CONH

SCHICHICOONB HO As SCHQ'CHICOON! A solution of the sodium salt of 3-acetylsulfonic acid is insoluble in alcohol, acetone,

or ether. It is quite readily soluble in water,

dilute hydrochloric acid, dilute alkalis, and

concentrated hydrochloric acid. It forms water-soluble salts with the alkali metals such as sodium and potassium, and wlth am- 2 nsOsogn omoom amino 4-hydroxyphenyl arsenious sulfo- 25 propionic acid shows a marked trypanocidal activity, and is less toxic than an amount of the arsenious' oxide containing the same quantity of arsenic; 3

Example 13. 5

grams of p-hydroxyphenylarsenious oxide,

HOOAFQ,

dissolved in a small volume of alcohol or acetone, isadded gradually with stirring a hot concentrated alcoholic solution containing L26 grams of pi-sulfhydrylbenzene sulfonic acid,

' ns Osom A precipitate starts forming immediately, and the mixed solutions are allowed to stand two or three hours at room temperature in order to complete the reaction. The iollowing reaction takes place 2-- monia; while the salts with the alkaline earth metals such as calcium are only moderately soluble in. water. The structural formula of 'the sodium salt is i A solution of the sodium salt of p-hydroxyphenyl arsenious sulfo benzene sulfonic acid shows a marked, trypano'cidal activity. 85

Example 14.

To 0.72 grams of 3-acetylamino 4-hydroxyphenyl arsenious oxide,

CH:CONH\ v HOOASO,

suspended or dissolved in c. c. alcohol, is

added gradually with stirring in alcoholic CHaCONIl The whitish precipitate, which is S-acetylamino thydroxyphenyl arsenious sulto ben zene sulfonic acid having ithe structural formula as indicated in the first term on the right-hand side of the foregoing reaction equation, is collccted on a filter, washed with alcohol, and dried in vacuo. W'hcn dry it is a palecream or white crystalline substance which does not melt or darken when heated to 300 C. It is soluble in water, dilute-hydrochloric acid, and dilute alkali. Itis practically insoluble in alcohol, acetone, and ether. It forms water-soluble salts with the alkali metals such as sodium and potassium, with ammonia, and with the alkaline-earth metals such as calcium. The structural formula of the sodium salt is omconn 0 A solution of the sodium salt of S-acetylamino 4-hydroxyphenyl arsenious sulfo benzene sulfonic acid shows a marked trypanocidal activity, and is less toxic than an amount of the arscnious oxide having the same quantity of arsenic.-

I claim as my invention 1. The step in the method of producing water-soluble compounds of organic arsenions compounds,.which eon'iprises treating, in a solvent. an arsenions compound in which. at least one valence bond of the arsenic is attached to an inorganic radical of other than the sulphur family (sulphur. selenium. and tellnrium) and at least one valence bond of the arsenic is directly attached to a carbon atom of an organic radical, with an organic compound containing both an acid radical and a sulfhydryl group and having the sult'hydryl group directly attached to a carbon atom.

2. The step in the method of producing 'ZIiBT-SOlllblE compounds of organic arseni- 2 IS-OSCBH omooNn solution containing 1.15 grams of dryl benzene sulfonic acid,

ns-O-soar.

A white precipitate forms during the addition of the sulfonic acid, and on continued stirring the reaction mixture becomes thick like a white paste. takes place 1-- s-O-som p-sulfhyous compounds, which comprises treating, in a solvent, an arsenious compound in which at least one valence bond of the arsenic is attached to an inorganic radical of other than the sulphur family (sulphur, selenium, and tellurium) and at least one valence bond of the arsenic is directly attached to a carbon atom of an organic radical of the aromatic series, witli'an organic compound containing both an acid radical and a sulfhydry] group and'having the sulfhydryl group directly attached to a carbon atom.

3. The step in the method of producing water-soluble compounds of organic arsenious compounds, which comprises treating, in a solvent, an arsenious compound in which at least one valence bond of the arsenic is attachedto on inorganic radical of other than the sulphurfamily (sulphur, selenium, and tellurium) and at least one valence bond of the arsenic is directly attached to a carbon atom of a substituted aromatic radical, with an organic. compound" containing both an acid radical and a snlfhydryl group and having the sulthydryl group directly attached to a carbon atom.

4. The step in the method of producing water-soluble compounds of organic arsenions compounds, which comprises treating, in

a solvent, an arscn'ious compound in which at least one valence bond of the arsenic is attached to an inorganic radical of other than the snlplnir family (sulphur, selenium, and telluriuni) and at least one valence bond of the arsenic is directly attached to a carbon atoin of a substituted phenyl radical, with an organic compound containing both an acid radical and a sulthydrvl group and having the snlfhydryl group directly attached to a carbon atom.

5. The step in the method of producing water-soluble compounds of organic arsenious compounds, which comprises treating, in a solvent. :1 compound of the formula R-As Y, in which Y CQmprises one or The following reaction more replaceable inor anic radicals or groups other than of t e sulphur family (sulphur, selenium, and tellurium) and having a total valence of two, and in which R is an organic radical having a carbon atom to which the arsenic is directly attached,

with an organic compound containing both.

an acid radical and a sulfhydryl group and having the sulfhydryl group directly attached to a carbon atom.

6. The step in the method of producing water-soluble compounds of organic arsenious compounds, which comprises treating, in a solvent, a compound of the formula RAs==Y, in which Y comprises one or replaceable inorganic radicals or groups other than of the sulphur family (sulphur, selenium, and tellurium) and hav 'ing a total valence of two, and in which R is a substituted aromatic radical having a carbon atom to which the arsenic is directly attached, with an organic compound containing both an acid radical and a sulfhydrvl group and having the sulfh 'dryl group dircctly attached to a carbon atom.

7. The step in the method of producing water-soluble compounds of organic arsenious compounds, which comprises treating, in a solvent, a compound of the formula RAs=O, in which R is an organic radical having a carbon atom to which the arsenic is directly attached, with an organic compound containing both an acid radical and a sulfhydryl group and having the sulfhydr vl group directlv attached to a carbon atom.

8. The step in the method of producing water-soluble compounds of organic arsenious compounds, which comprises treating, in a solvent, a compound of the .formula R As=.O, in which R is a substituted aromatic radical having a carbon atom to which the arsenic'is directly attached, with an organic 'compound containing both an acid radical and a sulfhydryl group and having the sulfhydryl group directly attached to a carbon atom.

9. An arsenious organic compound. in which at least one bond of a trivalentarsenic atom is attached to a carbon atom otnn organic radical, and at least one other bond of the trivalent arsenic atom is attached to a. sulphur atom, and the sulphur is also attached to a carbon atom of an organic radical containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

10. An arsenious organic compound. in which at least one bond of a trivalent arsenic atom is'attached to a carbon atom of an aromatic radical, and at least one other bond ofthe trivalent arsenic atom is attached to a sulphur atom, and the sulphur is also attached to a carbon atom of an organic radical containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

11. An arsenious organic compound, in which at leastone bond of a trivalent-arsenic atom is attached to a carbon atom of a substituted aromatic radical, and at least one other bond of the trivalent arsenic atom is attached to a sulphur a%m, and the sulphur is also attached to a car on atom of an organic radical containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

12. An arsenious organic compound, in which at least one bond of a trivalentarsenic atom is attached to a carbon atom of a substituted phenyl radical, and at least one other bond of the trivalent arsenic atom is attached to a. sulphur atom, and the sulphur is also attached to a carbon atom of an organic radical containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

13. A conipo ml containing the following radical:

S-Rnr- R s-m..

where R is any organic radical having a carbon atom directly attached to the arsenic, and R is an organic radical having a carbon atom directly attached to the sulphur atom and containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

14. A compound containing the following radical:

where R is an aromatic radical having a carbon atom directly attached to the arsenic, and R is an organic radical having a carbon atom directly attached to the sulphur atom and containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

15. A compound containing the following radical:

where R is a substituted aromatic radical having a carbon atom directly attached to the arsenic, and R is an organic radical having a carbon atom directly attached to the sulphur atom and containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

16. A compound containing the following where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is an organic radical having a carbon atom directly attached to the Sulwhere R is any organic radical having a carbon atom directly attached to the arsenic, and R is an organic radical which has a carbon atom directly attached to the sulfide sul hur atom and which is combinable with w an 0 group to form a sulfonic acid.

18. A compound containing the following radical:

R'-SO:-

where R is an aromatic radical having a carbon atom directly attached to the arsenic, and R is an organic radical which has a carbon atom directly attached to the sulfide sulphur atom and which is combinable with an S0 group to form a sulfonic acid.

19. A compound containing the following where R is a substituted aromatic radical having a carbon atom directly attached to the arsenic, and R is an organic radical which has a carbon atom directl attached to the sulfide sulphur atom an which is combinable with an SO group to form a sulfonic acid.

20. A compound containing the following where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is an organic radical which has a carbon atom directl attached to the sulfide sulphur atom an which is combinable with an S0, group to form a sulfonic acid. n

21. A compound containing the followmg radical: s CH so l 3 s-c.H4so,-'

in which R is any organic radical having a carbon atom directly attached to the arsenic. 22. A compound containing the following radical in whid'h R is a. substituted aromatic radical having a carbon atom directly attached to in which R is a substituted henyl radical having a carbon atom directly attached to the arsenic.

25. A compound containing the following radical:

R As 8-RA|: SRAZ where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is an aromatic radical having a carbon atom directly attached to the su phur atom and containing an acid group which has a freevalence bond capable of being attached either to hydrogen or to a metal.

26. A compound containing the following radical:

RAI R innwhere R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is a substituted aromatic radical having a carbon atom directly attached to the sulphur atom and containing an acid group which has a free valence bond capable of being attached either to hydrogen or to a metal.

27. A compound containing the followwhere R is a substituted phenyl radical haw ing a carbon atom directly attached to the arsenic, and R is an aromatic radical having a carbon atom of its nucleus directly attached to the sulphur atom and containing an acid group which has a free valence bond capable of bein attached either to hydrogen or to 9. meta 28. A compound containing the following radical: R

where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is a substituted aromatic radical havin a carbon atom of its nucleus directly attac ed to the sul hur atom and containing an acid group w ich has a free valence bond capable of being attached either to hydrogen or to a metal.

29. A compound containing the following radical:

where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is an aromatic radical combinable with a SO group to form a sulfonic acid and having a carbon atom directly attached to the sulfide sulphur atom.

30. A compound containing the following radical s-a'so,-

where R is a substituted plienyl radical having a carbon atom directly attached to the arsenic, and It is a substituted aromatic radical combinable with a St), group to form a sulfonic acid and havin a carbon atom directly attached to the sol ide sulphur atom.

31. A compound containing the following radical:

S-RSO where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is a substituted aromatic radical combinable with a SO, group to form a sulfonic acid and having a carbon atomof its nucleus directly attached to the sulfide sulphur atom.

33. A Water-soluble compound containing the following radical:

NHGOCHa 34. A water-soluble compound having the following formula:

SOsNo As SO|N3 NHCOCH;

In witness whereof, I have hereunto set my hand at College Park, Maryland, this 19th day of January, A. D. one thousand nine hundred and twent seven.

MORRIS KHARASCH.

CERTIFICATE OF CORRECTION.

Patent No. l, 677, 392.

Granted July 17, 1928, to

MORRIS S. KHARASCH.

It is hereby certified that error appears in the above numbered patent grant, and in the heading to the printed specilug correction as follows: in the fication, the residence of Park, Indiana", whereas "College Park, Maryland";

the patentee is erroneously written said residence should have been written and printed as page 6, line97, after requirand printed "College "HO-126" insert the capital letter "C"; page 10, in the upper right hand corner of formula 35, the radical Patent should be readwith these correc line 10, for the'word "in" H" instead of with a vertical line preceding the letread "an"; and that the said Letters tions therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 14th day of January,

(Seal) v M. J. Moore, Acting Commissioner of Patents.

arsenic, and R is an aromatic radical combinable with a SO group to form a sulfonic acid and having a carbon atom directly attached to the sulfide sulphur atom.

30. A compound containing the following radical s-a'so,-

where R is a substituted plienyl radical having a carbon atom directly attached to the arsenic, and It is a substituted aromatic radical combinable with a St), group to form a sulfonic acid and havin a carbon atom directly attached to the sol ide sulphur atom.

31. A compound containing the following radical:

S-RSO where R is a substituted phenyl radical having a carbon atom directly attached to the arsenic, and R is a substituted aromatic radical combinable with a SO, group to form a sulfonic acid and having a carbon atomof its nucleus directly attached to the sulfide sulphur atom.

33. A Water-soluble compound containing the following radical:

NHGOCHa 34. A water-soluble compound having the following formula:

SOsNo As SO|N3 NHCOCH;

In witness whereof, I have hereunto set my hand at College Park, Maryland, this 19th day of January, A. D. one thousand nine hundred and twent seven.

MORRIS KHARASCH.

CERTIFICATE OF CORRECTION.

Patent No. l, 677, 392.

Granted July 17, 1928, to

MORRIS S. KHARASCH.

It is hereby certified that error appears in the above numbered patent grant, and in the heading to the printed specilug correction as follows: in the fication, the residence of Park, Indiana", whereas "College Park, Maryland";

the patentee is erroneously written said residence should have been written and printed as page 6, line97, after requirand printed "College "HO-126" insert the capital letter "C"; page 10, in the upper right hand corner of formula 35, the radical Patent should be readwith these correc line 10, for the'word "in" H" instead of with a vertical line preceding the letread "an"; and that the said Letters tions therein that the same may conform to the record of the case in the Patent Office.

Signed and sealed this 14th day of January,

(Seal) v M. J. Moore, Acting Commissioner of Patents. 

